In 1953, adenoviruses were separated from a culture solution of pediatric tonsil or adenoid cells. The existence of 80 or more adenovirus serotypes that are infected with humans, birds, cattle, monkeys, dogs, mice, or pigs as a host has been discovered to date. Up to the present, 51 or more types of adenovirus serotypes that are infected with humans as a host have been discovered, and adenovirus type 2 and type 5 are used as vectors for gene therapy.
Adenovirus type 5 is a non-enveloped and regular icosahedron with 252 capsomeres. Among them, the 12 capsomeres located at the peak of the icosahedron are referred to as “pentons” (composed of Penton bases and fibers) having projected structures and the other 240 capsomeres are referred to as “hexons.” Viruses infiltrate (infect) cells as follows. Fibers bind to the CAR receptors (for details, please refer to Bergelson J M et al., Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5, Science 275: 1320-1323, 1997) and the RGD motifs of the penton bases then bind to the integrins on the cell surfaces (Bai M, Harfe B, Freimuth P, Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells, J. Virol. 67: 5198-5205, 1993; Wickham T J et al., Integrins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment, Cell 73: 309-319, 1993). Viruses that reach the endosomes alter capsid protein structures under acidic conditions, disrupt the endosomes, and infiltrate the cytoplasm. Accordingly, the first step of infection is the binding of viral fibers to the CAR receptors on the cell surfaces, and the infection range for a vector is considered to be capable of being varied via modification of fibers (Paillard, F., Dressing up adenoviruses to modify their tropism, Hum. Gene Ther. 10:2575-2576, 1999).
Adenovirus type 35 was first discovered in urine of patients such as those who had undergone kidney transplantation, those who had undergone marrow graft, and those with AIDS. Infection therewith is said to cause acute hemorrhagic cystitis and to infect the kidney. At present, a receptor for adenovirus type 35 infection is not yet known.